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Ruman Rahman

Associate Professor of Molecular Neuro-Oncology, Faculty of Medicine & Health Sciences

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Biography

After graduating with a BSc in Genetics from the University of Edinburgh, Dr. Rahman completed a PhD in Molecular Biology at the Roslin Institute, University of Edinburgh under the supervision of Sir Ian Wilmut in 2007. He joined the Children's Brain Tumour Research Centre (CBTRC), University of Nottingham as a Post-Doctoral Research Associate in 2007, where a research highlight identified Nucleolin as a prognostic marker in paediatric ependymoma (Neuro-Oncology 10: 675-689, 2008).

After receiving the Nottingham Advanced Research Fellowship for the Faculty of Medicine in 2011, Dr. Rahman was appointed Assistant Professor at the University of Nottingham's School of Medicine in October 2013 and awarded the British Neuro-Oncology Society Young Investigator of the Year in 2014.

He currenty leads research programmes in neurosurgically-applied drug delivery, brain tumour heterogeneity and brain tumour metabolism as Associate Professor, with a grant portfolio of £6M since 2013. Key international collaborations include Johns Hopkins University, Mayo Clinic and University of Louvain, with a research highlight demonstrating a long-term survival benefit in orthotopic brain tumour models when combined chemotherapeutics are delivered at neurosurgery via a biodegradable paste (Clinical Cancer Research 25(16): 5094-5106, 2019).

His affiliation to professional bodies includes membership on the Evaluation Committee for the French National Institute of Health and Medical Research (INSERM) (2019-present), Society for Neuro-Oncology Conference Scientific Review Committee (2016-present), British Neuro-Oncology Society Research Sub-Committee (2018-present) and he is an editorial board member for Scientific Reports. He is currently Chair for the 'Children with Cancer UK' funded Children's Brain Tumour Drug Delivery Consortium which spans leading institutions across Europe and North America (including Johns Hopkins University and the National Cancer Institute) (2021-2023) and co-Chair of the British Neuro-Oncology Society Research Subcommittee (2021-2023)

Expertise Summary

Molecular and cellular neuro-oncology; biomaterial-based drug delivery.

Teaching Summary

Lecturing - 12 lectures (1 PhD, 7 BSc, 4MSc) across 7 modules.

University of Nottingham:

  • Neuro-Oncological Application of Tissue Engineering Concepts - Tissue Engineering Course - CDT Regen Med (2017-present).
  • Brain Cancer Future Medicines Seminar - BSc Biochemistry and Molecular Medicine, Year 3 Advanced Biochemistry of Cancer module (2016-present).
  • Cancer Chemotherapy - Pre-Clinical/Clinical (BSc Biochemistry and Molecular Medicine, Year 3 Advanced Biochemistry of Cancer module (2015-present).
  • Cancer Evolution I: Principles (BSc Biochemistry of Cancer C74CAN, Year 3 Advanced Biochemistry of Cancer module (2016-present).
  • Cancer Evolution II: Application (BSc Biochemistry of Cancer C74CAN, Year 3 Advanced Biochemistry of Cancer module (2015-present).
  • Biology of Metastasis - Adhesion Molecules and Cell-Cell/Matrix Interactions 1 (Migration) (MSc Oncology, A34C02/L/05 Tumour Physiology) (2015-present).
  • Biology of Metastasis - Adhesion Molecules and Cell-Cell/Matrix Interactions 2 (Invasion) (MSc Oncology, A34C02/L/05 Tumour Physiology) (2015-present).
  • Tumours of the Brain (BSc Graduate Entry Medicine BMBS) (2015 - present).
  • Biomaterials and Cancer Therapeutics (BSc Medical Physiology and Therapeutics - 3rd Year Cancer Biology Module) (2014 - present). (Setting, marking and moderating MCQ/SAQ for ~35 students).
  • Localised drug delivery for brain cancer (BSc Medical Physiology and Therapeutics - 3rd Year Cancer Biology Module) (2014 - present).
  • Leukaemic Stem Cells (MSc. Stem Cell Technology) (2012-present).

Keele Medical School:

  • Stem Cells in Cancer (MSc. 'Cell and Tissue Engineering' (2007-present).

Research Summary

My research group are broadly interested in two research themes: 1) Molecular Neuro-Oncology; 2) Brain tumour drug delivery.

1) Molecular Neuro-Oncology:

We have established dynaimc 3D brain tumour culture models using the NASA-developed Rotary Cell Culture System (RCCS). The molecular biology and genetics of brain tumour cells grown as 3D cultures better resembles the biology of the patients' tumour, when compared to traditional 2D cultures. We are now using this culture system to test the effectiveness of novel candidate anti-cancer drugs, thus avoiding the requirement to test such drugs in animals in the first instance.

We are also aiming to identify whether the biology of a brain tumour called glioblastoma (GBM), varies in different regions within each tumour (intratumour heterogeneity). Through a precise reading of the information carried in GBM DNA, we will spot 'errors' (mutations) that enable the cancer to survive. Similarly, by reading the information carried in GBM RNA, we will identify genes incorrectly switched on. A key goal will be to combine data on mutations and genes from different parts of the tumour to reveal which mutations are crucial to its survival. If these genes are identified, the proteins involved will also be known. Drugs that target these proteins will be tested on GBM cells grown in the RCCS and in mice with GBM tumours.

To complement our genome wide genetic mutation and gene expression analyses, my group is also developing a functional genomics approach to study GBM intra-tumour heterogeneity. Specifically we are conducting phospho-proteomics and metabolomics using advanced mass spectrometry methods.

2) Brain tumour drug delivery:

Current methods to deliver cancer chemotherapy drugs results in drugs reaching all parts of the body, causing the death of healthy cells. This also means that the amount of drug that reaches the tumour may not be enough to destroy it. We have evaluated a new drug delivery system which uses polymer microparticles to deliver drugs directly to the site of the tumour at the time of surgery, thereby targeting cancer cells that are often left behind and reducing drug-related side-effects throughout the body.The opportunity to deliver cancer drugs locally within the tumour resection cavity bypasses the blood-brain-barrier, targeting micro-deposits of neoplastic cells that remain following tumour resection. This has the potential to achieve a high effective dose locally whilst maintaining a low toxic dose systemically.

Selected Publications

PRIZES

British Neuro-Oncology Society Conference - Best Oral Presentation Jul 2015 (1st).

School of Medicine Clinical Showcase - Best Poster Prize, Apr 2015 (1st).

British Neuro-Oncology Society Young Investigator Award 2014 (* Highest national accolade in the field of neuro-oncology for basic or clinical scientists under the age of 35).http://blogs.nottingham.ac.uk/pressoffice/2014/07/09/national-award-for-innovative-nottinghamresearcher/

Genetics Society international writing competition, 2004 (1st) (Rahman R. "The Stems of Cancer".Genetics Society Newsletter 2005; (52) 50-52).

INVITED TALKS

UK-Nordic Proteoglycan Conference (Uppsala, Sweden, 03/05/2023) - Title: Recapitulating post-surgical brain tumour microenvironments using human decellularized brain extracellular matrix.

(Invited Speaker) British-Iberian Bioelectronics Workshop (BIBio-e) (Instituto Superior Tecnico, Lisbon, Portugal, 17/02/23). Title: Harnessing bioelectronics as a new treatment modality for malignant brain cancer.

(Invited Plenary Speaker) IV International Congress in Health Sciences Research (University of Beira Interior, Covilha, Portugal, 13/02/23) - Title: Targeting glioblastoma infiltrative disease through a Darwinian lens.

Society for Image-Guided Neurointerventions (SIGN) Conference (Warwick Castle, 22/08/2022). Session: Bioscaffolds; Title: Polymer-based neurosurgically applied interstitial drug delivery for malignant glioma.

Department of Chemistry (Lancaster University, 27/07/2022) - Targeting glioblastoma residual disease using drug delivery systems applied at neurosurgery.

British Neuro-Oncology Society (Liverpool, 23/06/2022) - Session: Basic Science II. Title: Spatially resolved transcriptomics reveal unique defining molecular features of infiltrative tumour cells associated with glioblastoma recurrence.

Faculty of Science, Technology, Engineering and Mathematics Open University, School of Life, Health and Chemical Sciences, 07/06/2022) - Title: Characterisation and therapeutic targeting of glioblastoma infiltrative disease.

Cardiff University, School of Pharmacy & Pharmaceutical Sciences (Cardiff, 04/05/2022) - Targeting glioblastoma residual disease using drug delivery systems applied at neurosurgery.

Collaborative Network for Neuro-Oncology Clinical Trials (CONNECT) Consortium (Virtual (UK/US/Australian members, 05/04/2022) - Title: Pre-clinical models/Children's Brain Tumour Drug Delivery Consortium.

Leeds Institute of Medical Research (University of Leeds, 03/02/2022) - Title: Characterisation and therapeutic targeting of glioblastoma infiltrative disease.

Society for Neuro-Oncology (Boston, Massachusetts, 20/11/2021) - Session: Molecular Pathology; Title: Spatial-transcriptomics reveals unique molecular features of fluorescence-sorted 5-aminolevulinic acid+ infiltrative tumor cells associated with recurrence and poor survival in glioblastoma.

Children's Cancer & Leukaemia Group - Childhood Cancer Conference (Virtual) - (17/10/21) - Delivering chemotherapy to malignant childhood brain cancers using a biodegradable paste.

Society for Neuro-Oncology Paediatric Neuro-Oncology Conference (Washington DC/Virtual) - (10/11/2021) Moderator Session 2 - Synaptic signalling in paediatric brain tumours. (11/11/2021) Invited speaker and Session Chair - Session: Overcoming challenges to CNS therapeutic drug delivery for paediatric neuro-oncology - Title: Evolving strategies for efficacious drug penetration in paediatric brain tumours.

University of Santiago de Compostela, Centre for Research in Molecular Medicine and Chronic Diseases (Invited seminar) (30/10/2020) - Targeting malignant glioma infiltration.

Brain Tumour Charity (Invited Webinar) (21/10/2020) - Revealing hidden gene signatures for infiltrative glioblastoma using 5ALA.

University of Cambridge, Electrical Engineering Division (Invited seminar) (22/06/2020) - Title: Targeting glioblastoma residual disease using neurosurgically-applied drug delivery systems.

University of Nottingham Biochemistry Society Public Lecture - (Nottingham, 23/01/2020) - Title: Brain cancer through a Darwinian lens.

British Neuro-Oncology Society (London, 04/07/2019) - Session: Adult intrinsic tumours; clinical. Title: Neurosurgical delivery of the ADP ribose polymerase-1 inhibitor olaparib from a thermo-responsive biodegradable paste potentiates radiotherapy and prolongs survival.

Society for Image-Guided Neurointerventions (SIGN) Conference (Baltimore, 10/06/2019). Session: Opening Ceremony; Title: The Children's Brain Tumour Drug Delivery Consortium.

Society for Image-Guided Neurointerventions (SIGN) Conference (Baltimore, 11/06/2019). Session: Biomaterials and Nanotechnologies; Title: A neurosurgically-applied thermo-sensitive paste for the delivery of brain tumour chemo- and nano-therapies.

Children with Cancer UK 'Child and Teens/Young Adults' Conference (Westminster, London, 14/09/2018) - Title: Update on the Children's Brain Tumour Drug Delivery Consortium.

International Symposia for Pediatric Neuro-Oncology (Denver, Colorado, 02/07/2018) - Session: Drug Delivery; Title: The Children's Brain Tumour Drug Delivery Consortium.

Institute for NanoBio Technology, Johns Hopkins University, School of Medicine (Baltimore USA, 31/10/2017) - Multi-agent neurosurgical application of a chemotherapeutic paste in the treatment of malignant glioma.

Strathclyde Institute of Pharmacy and Biomedical Sciences (Glasgow, 06/10/2017) - Neurosurgical application of a polymeric paste for chemotherapy delivery in the treatment of malignant glioma.

Children with Cancer UK Precision Medicine in Childhood Cancer - (Newcastle, 18/09/2017) - Session: Introduction and Progress Update; Title: Children's Brain Tumour Drug Delivery Consortium.

Academy of Pharmaceutical Sciences - (University of Hertfordshire, 06/09/2017) - Session: Crossing the disciplinary divide for improved healthcare (sponsored by UK & Ireland Controlled Release Society; Title: Neurosurgical application of a polymeric paste for chemotherapy delivery in the treatment of malignant glioma.

British Science Association Public Lecture - (University of Nottingham, 20/07/2017) - Title: Darwin's Oncology Legacy.

Glioma Invasion Forum - (Piran, Slovenia, 25/04/2017) - Title: Genetic and metabolic signatures of the glioma margin.

Society for Neuro-Oncology (San Antonio, 20/11/2015) - Delineating intra-tumour metabolomic and phospho-proteomic heterogeneity in glioblastomas through advanced analytical methods.

Departments of Oncology and Stem Cell Research - (Imperial College London, 27/11/14). (Seminar) Glioma heterogeneity: from modeling to therapy.

British Neuro-Oncology Society (University of Liverpool, 03/07/2014) - Title: Glioma heterogeneity: from modeling to therapy. * Young Investigator Award Prize Lecture.

Society for Neuro-Oncology Basic and Translational Research (Fort Lauderdale, 16/05/2013) - Session: High Grade Glioma; Title: VEGF/FGF-dependent vasculogenic mimicry and tumor-derived angiogenic response in high grade glioma.

International Symposia for Pediatric Neuro-Oncology (Toronto, 26/06/2012) - Session: Advances in Neurosurgery; Title: Adjuvant chemotherapy for brain tumors delivered via a novel intra-cavity moldable polymer matrix.

Society for Neuro-Oncology Basic and Translational Research (New Orleans, 19/05/2011) - Session: High Grade Glioma and Ependymoma; Title: Evaluating novel polymeric microparticle-based injectable matrices for local chemotherapeutic delivery.

British Neuro-Oncology Society (University of Cambridge, 01/07/2011) - Title: Evaluating novel polymeric microparticle-based injectable matrices for local chemotherapeutic delivery.

Past Research

I have studied the role of the telomere and telomerase pathways with respect to childhood brain cancer progression, particularly with respect to targeting telomerase as a potential mode of therapy. I have investigated the role of histone deacetylase inhibition using Trichostatin A in high grade paediatric tumours and have shown distinct telomerase inhibition associated with anti-proliferative and pro-apoptotic cellular effects. Additionally, I have evaluated the role of the G4 quadruplex ligand, RHPS4 in indirectly inhibiting telomerase by restricting access to the telomere. I am also interested in determining the contribution of dysregulated stem-like cells to childhood brain tumours and understanding mechanisms of resistance such cells may harbour; e.g.- cellular quiescence.

Future Research

Functional Genomic Characterisation of Intra-glioma Heterogeneity

To complement our genome wide genetic mutation and gene expression analyses, my group is also developing a functional genomics approach to study GBM intra-tumour heterogeneity. Specifically we are conducting phospho-proteomics and metabolomics using advanced mass spectrometry methods. We hypothesise that active proteins and metabolites predominant at the glioma invasive margin, represent clinically-relevant targets for therapy. We will develop orthotopic patient-derived xenografts using cells isolated from the invasive margin, thus representing a pre-clinical tailored pharmacological framework.

3D Cell Culture Models of Brain Tumours

We aim to assess whether these models are able to predict drug response in animals and in patients receiving identical therapy and use this system to test the anti-cancer effects of a new group of drugs called histone deacetylase inhibitors.

Local Drug Delivery for Brain Tumours

We aim to evaluate efficacy and neurotoxicity of our polymer-based drug delivery system in vivo. Additionally we will further develop the biomaterials approach to demonstrate greater flexibility in tailoring drug release profiles.

School of Medicine

University of Nottingham
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